The Department of Energy (DOE)-National Cancer Institute (NCI) Exascale Initiative is a collaboration formed to jointly accelerate federal missions in precision oncology and computing through an alignment of needs, and has been driven by three key national initiatives: the National Strategic Computing Initiative, the Precision Medicine Initiative, and the Beau Biden Cancer Moonshot. NCI has a critical need for increased computational capacity and sophisticated computational models to identify promising new treatments; deepen understanding of cancer biology; understand the impact of new diagnostics, treatments, and patient factors in cancer outcomes at the individual patient level; and to integrate pre-clinical model data for cancer research, diagnosis and treatment. DOE has a need for partnerships with user communities to broaden the functionality of next-generation high-performance computers and to advance the DOE mission in low dose radiation and systems biology for energy applications. The DOE-NCI collaboration brings together the HPC expertise and resources of the DOE with the NCI cancer biology and oncology knowledge base, infrastructure and data repositories to support accelerating capable exascale computing technologies and advance the frontiers of precision oncology, computational and data science, and advanced computing applied to cancer.